Characterization of tumor angiogenesis in rat brain using iron-based vessel size index MRI in combination with gadolinium-based dynamic contrast-enhanced MRI

J Cereb Blood Flow Metab. 2009 Oct;29(10):1714-26. doi: 10.1038/jcbfm.2009.86. Epub 2009 Jul 8.


This study aimed at combining an iron-based, steady-state, vessel size index magnetic resonance imaging (VSI MRI) approach, and a gadolinium (Gd)-based, dynamic contrast-enhanced MRI approach (DCE MRI) to characterize tumoral microvasculature. Rats bearing an orthotopic glioma (C6, n=14 and RG2, n=6) underwent DCE MRI and combined VSI and DCE MRI 4 h later, at 2.35 T. Gd-DOTA (200 mumol of Gd per kg) and ultrasmall superparamagnetic iron oxide (USPIO) (200 micromol of iron per kg) were used for DCE and VSI MRI, respectively. C6 and RG2 gliomas were equally permeable to Gd-DOTA but presented different blood volume fractions and VSI, in good agreement with histologic data. The presence of USPIO yielded reduced K(trans) values. The K(trans) values obtained with Gd-DOTA in the absence and in the presence of USPIO were well correlated for the C6 glioma but not for the RG2 glioma. It was also observed that, within the time frame of DCE MRI, USPIO remained intravascular in the C6 glioma whereas it extravasated in the RG2 glioma. In conclusion, VSI and DCE MRI can be combined provided that USPIO does not extravasate with the time frame of the DCE MRI experiment. The mechanisms at the origin of USPIO extravasation remain to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / diagnosis
  • Cell Membrane Permeability
  • Contrast Media
  • Dextrans / pharmacokinetics
  • Ferrosoferric Oxide / pharmacokinetics
  • Gadolinium / pharmacokinetics*
  • Glioma / diagnosis
  • Glioma / pathology
  • Heterocyclic Compounds / pharmacokinetics
  • Iron / pharmacokinetics*
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles
  • Male
  • Microvessels
  • Neovascularization, Pathologic / diagnosis*
  • Organometallic Compounds / pharmacokinetics
  • Rats
  • Rats, Wistar


  • Contrast Media
  • Dextrans
  • Heterocyclic Compounds
  • Magnetite Nanoparticles
  • Organometallic Compounds
  • ferumoxtran-10
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
  • Gadolinium
  • Iron
  • Ferrosoferric Oxide